First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases

Abstract

Background: It is well known that second-trimester maternal serum alpha-fetoprotein (MS-AFP) is a predictor for adverse pregnancy outcomes (APOs), such as preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). However, it is unknown whether first-trimester MS-AFP is also predictive of APOs. Methods: We retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of APOs regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders. Results: A total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), and had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000), but the actual between-group differences were minuscule. The areas under ROC curves were 0.572 (P = 0.001), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, preeclampsia and SGA, respectively. Subdivisions for the disorders did not obviously improve the performances of MS-AFP. Conclusions: Elevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.

Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

“…Based on the long-term screening programs used to detect neural tube defects and fetuses with DS, it was determined that the AFP norms in maternal serum range from 0.5 to 2.5 MoM in the first and second trimester [32,33]. Until the 1970s, AFP detection was widely carried out by immunoelectrophoresis, which is a method focusing on qualitative determination and does not produce accurate results.…”

Maternal First-Trimester Alpha-Fetoprotein and Placenta-Mediated Pregnancy Complications

“…Data regarding the association of first-trimester AFP with placenta-mediated complications have thus far been limited, given that information on this marker has 31,[42][43][44][45][46] In addition, available studies have yielded conflicting results, are relatively small (sample sizes range between 1068 and 17 071 women), and mostly did not include a comparison positive-control group of second-trimester AFP or the traditional first-trimester serum markers such as PAPP-A. 44,45 For example, in a prospective study of 4659 nulliparous women that aimed to develop a first-trimester prediction model for preterm preeclampsia, first-trimester AFP (but not PAPP-A) was among the 4 variables that were selected for the final model (along with mean arterial blood pressure, PlGF, and uterine artery Doppler). 42 Similarly, in a recent retrospective study of 1280 patients, Dinglas et al 45 reported that although first-trimester AFP was not associated with the primary outcome of preeclampsia, it was associated with some of the secondary outcomes, such as fetal growth restriction and preterm birth.…”

“…[32][33][34][35][36][37][38][39][40][41][42] In addition, most studies have not directly compared the strength of these associations between elevated first-trimester and second-trimester AFP. 31,[42][43][44][45][46] Based on the presumed mechanism underlying the association of AFP with placental complications (increased placental permeability, which may increase progressively with gestational age in pregnancies with abnormal placentation), we hypothesized that the predictive accuracy of first-trimester AFP would be lower than that observed for second-trimester AFP. 47 Therefore, our objective was to estimate the association of first-trimester AFP with placenta-mediated pregnancy complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers in a large provincial population-based cohort of unselected women with viable singleton pregnancies.…”

Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction

“…The addition of UtA-PI measurement further improved detection rates of SGA infants to 78% at 32–36 weeks and 42% at >37 weeks, respectively [ 46 ]. Another retrospective study [ 47 ] showed that while elevated serum AFP concentrations (≥2.5 MoM) in the first trimester was associated with birth of an SGA infant, its predictive utility for SGA and FGR was low with an AUROC of <0.6 [ 47 ]. Similarly, other studies have also demonstrated that although third trimester AFP concentrations are significantly lower in women with SGA infants, the overall detection rate using this biomarker is low at 26%, and even when it is combined with maternal PlGF concentrations detection rates only modestly increase to 32% [ 48 ].…”